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Abstract Monoterpenoid indole alkaloid (MIA) biosynthesis in Catharanthus roseus is a paragon of the spatiotemporal complexity achievable by plant specialized metabolism. Spanning a range of tissues, four cell types, and five cellular organelles, MIA metabolism is intricately regulated and organized. This high degree of metabolic differentiation requires inter-cellular and organellar transport, which remains understudied. Here, we have characterized a vacuolar importer of secologanin belonging to the multidrug and toxic compound extrusion (MATE) family, named CrMATE1. Phylogenetic analyses of MATEs suggested a role in alkaloid transport for CrMATE1, and in planta silencing in two varieties of C. roseus resulted in a shift in the secoiridoid and MIA profiles. Subcellular localization of CrMATE1 confirmed tonoplast localization. Biochemical characterization was conducted using the Xenopus laevis oocyte expression system to determine substrate range, directionality, and rate. We can confirm that CrMATE1 is a vacuolar importer of secologanin, translocating 1 mM of substrate within 25 min. The transporter displayed strict directionality and specificity for secologanin and did not accept other secoiridoid substrates. The unique substrate-specific activity of CrMATE1 showcases the utility of transporters as gatekeepers of pathway flux, mediating the balance between a defense arsenal and cellular homeostasis.

BackgroundSingle photon emission computed tomography (SPECT) is becoming increasingly popular in oncology. This study endeavors to scrutinize the radiation protection knowledge, attitude, and practice (KAP) exhibited by healthcare professionals involved in this imaging modality.MethodsThis cross-sectional study was conducted between September 23, 2023, and October 23, 2023, at the Second Affiliated Hospital of Anhui Medical University, the First Affiliated Hospital of Anhui Medical University, and the People’s Hospital of Liuan. Demographic data and KAP scores were acquired through the administration of questionnaires.ResultsA total of 450 healthcare professionals participated in the study. Correlation analyses revealed significant positive correlations between knowledge and attitude, knowledge and practice, as well as attitude and practice. Multivariate analysis indicated that being over 40 years old was independently associated with good knowledge, as well as positive attitudes. Occupations as nurses and having no contact with SPECT patients were independently associated with a lower level of knowledge, as well as negative attitudes. Furthermore, being female, having an occupation as a nurse, and not having received relevant training were independently associated with negative practice.ConclusionOncology healthcare professionals had suboptimal knowledge, negative attitude and inactive practice towards radiation protection in SPECT.

Exposure to benzene causes acute myelosuppression and other hematologic disorders. However, the detailed mechanism by which benzene exerts its severe hematotoxicity and potential treatments still require further deciphering and exploration. Herein, we found that hydroquinone (HQ), a main benzene metabolite, significantly increased intracellular reactive oxygen species (ROS) formation and subsequently caused damage to DNA, leading to impaired colony formation capacity and induction of apoptosis in human hematopoietic stem/progenitor cells (HSPCs) in vitro. The effects were mediated by activation of Src kinase, which subsequently activated the p38 signaling pathway while inhibiting the Akt signaling pathway. The mechanism was further verified by pre-treatment with a Src kinase inhibitor SKI-606, which effectively reversed the dampened self-renewal capacity and increased apoptosis of HSPCs induced by HQ in vitro. Furthermore, administration of SKI-606 partially reversed benzene-induced hematotoxicity and prolonged the survival time in benzene-poisoned mice. Taken together, these findings highlight that HQ-induced hematotoxicity in HSPCs is attributed to the Src kinase-mediated activation of p38 signaling pathway and repression of Akt signaling pathway. Notably, SKI-606 as a tyrosine kinase inhibitor may be a promising and potential agent for alleviating benzene-induced hematotoxicity.

Abstract Human visual neurons rely on event-driven, energy-efficient spikes for communication, while silicon image sensors do not. The energy-budget mismatch between biological systems and machine vision technology has inspired the development of artificial visual neurons for use in spiking neural network (SNN). However, the lack of multiplexed data coding schemes reduces the ability of artificial visual neurons in SNN to emulate the visual perception ability of biological systems. Here, we present an artificial visual spiking neuron that enables rate and temporal fusion (RTF) coding of external visual information. The artificial neuron can code visual information at different spiking frequencies (rate coding) and enables precise and energy-efficient time-to-first-spike (TTFS) coding. This multiplexed sensory coding scheme could improve the computing capability and efficacy of artificial visual neurons. A hardware-based SNN with the RTF coding scheme exhibits good consistency with real-world ground truth data and achieves highly accurate steering and speed predictions for self-driving vehicles in complex conditions. The multiplexed RTF coding scheme demonstrates the feasibility of developing highly efficient spike-based neuromorphic hardware.

Abstract Using updated National Health and Nutrition Examination Survey (NHANES) follow-up data, and a large nationwide representative sample of adult U.S. citizens, the aim of this study was to explore the relationship between dietary flavonol intake, all-cause and cause-specific mortality risks. In this prospective cohort study based on NHANES (2007–2008, 2009–2010, and 2017–2018), a total of 11,679 participants aged 20 years and above were evaluated. The amount and type of food taken during a 24-h dietary recall were used to estimate dietary flavonol intake, which includes total flavonol, isorhamnetin, kaempferol, myricetin, and quercetin. Each analysis of the weighted data was dealt with in accordance with the NHANES reporting requirements' intricate stratification design. The Cox proportional risk regression model or Fine and Gray competing risks regression model were applied to evaluate all-cause and cause-specific mortality risks, respectively. The follow-up period was calculated using the time interval between the baseline and the death date or December 31, 2019 (whichever occurs first). Each data analysis was performed between October 1, 2023, and October 22, 2023. Dietary flavonol intake included total flavonol, isorhamnetin, kaempferol, myricetin, and quercetin. Up to December 31, 2019, National Death Index (NDI) mortality data were used to calculate mortality from all causes as well as cause-specific causes. A total of 11,679 individuals, which represents 44,189,487 U.S. non-hospitalized citizens, were included in the study; of these participants, 49.78% were male (n = 5816), 50.22% were female (n = 5, 863); 47.56% were Non-Hispanic White (n = 5554), 18.91% were Non-Hispanic Black (n = 2209), 16.23% were Mexican American (n = 1895), and 17.30% were other ethnicity (n = 2021); The mean [SE] age of the sample was 46.93 [0.36] years, with a median follow-up of 7.80 years (interquartile range, 7.55–8.07 years). After adjusting covariates, Cox proportional hazards models and fine and gray competing risks regression models for specific-cause mortality demonstrated that total flavonol intake was associated with all-cause (HR 0.64, 95% CI 0.54–0.75), cancer-specific (HR 0.45, 95% CI 0.28–0.70) and CVD-specific (HR 0.67, 95% CI 0.47–0.96) mortality risks; isorhamnetin intake was associated with all-cause (HR 0.72, 95% CI 0.60–0.86), and cancer-specific (HR 0.62, 95% CI 0.46–0.83) mortality risks; kaempferol intake was associated with all-cause (HR 0.74, 95% CI 0.63–0.86), and cancer-specific (HR 0.62, 95% CI 0.40–0.97) mortality risks; myricetin intake was associated with all-cause (HR 0.77, 95% CI 0.67–0.88), AD-specific (HR 0.34, 95% CI 0.14–0.85), and CVD-specific (HR 0.61, 95% CI 0.47–0.80) mortality risks; quercetin intake was associated with all-cause (HR 0.66, 95% CI 0.54–0.81), cancer-specific (HR 0.54, 95% CI 0.35–0.84), and CVD-specific (HR 0.61, 95% CI 0.40–0.93) mortality risks; there was no correlation observed between dietary flavonol intake and DM-specific mortality. According to the current study, all-cause, AD, cancer, and CVD mortality risks declined with increased dietary flavonoid intake in the U.S. adults. This finding may be related to the anti-tumor, anti-inflammatory, and anti-oxidative stress properties of flavonol.

CD44 is a ubiquitous leukocyte adhesion molecule involved in cell-cell interaction, cell adhesion, migration, homing and differentiation. CD44 can mediate the interaction between leukemic stem cells and the surrounding extracellular matrix, thereby inducing a cascade of signaling pathways to regulate their various behaviors. In this review, we focus on the impact of CD44s/CD44v as biomarkers in leukemia development and discuss the current research and prospects for CD44-related interventions in clinical application.

The borosilicate glass was used to join reaction bonded silicon carbide through two steps, namely: laser cladding and low-temperature heat treatment. The wettability and microstructure of the laser cladding glass layer were examined, while joint microstructure and strength were analyzed at various temperatures and times. The results show that the laser cladding layer improved the wetting of glass on the substrate, formed a good interfacial bond, and reduced the joining temperature. The joints primarily consist of the glass phase, the boron-rich phase, and a few crystals. The high-strength joints obtained after heating the joint interface at 950 °C for 30 min had a flexural strength of 250 ± 20 MPa, a 68% improvement compared with direct connection under the same conditions. The joints also exhibit good thermal shock resistance and high-temperature strength. At 400 °C (thermal shock temperature) and 600 °C (test temperature), the residual flexural strengths were 122 ± 25 and 152 ± 12 MPa, respectively.

Abstract Background The previous studies have revealed that abnormal RNA-binding protein Musashi-2 (MSI2) expression is associated with cancer progression through post-transcriptional mechanisms, however mechanistic details of this regulation in acute myeloid leukemia (AML) still remain unclear. Our study aimed to explore the relationship between microRNA-143 (miR-143) and MSI2 and to clarify their clinical significance, biological function and mechanism. Methods Abnormal expression of miR-143 and MSI2 were evaluated in bone marrow samples from AML patients by quantitative real time-PCR. Effects of miR-143 on regulating MSI2 expression were investigated using luciferase reporter assay. Functional roles of MSI2 and miR-143 on AML cell proliferation and migration were determined by CCK-8 assay, colony formation, and transwell assays in vitro and in mouse subcutaneous xenograft and orthotopic transplantation models in vivo. RNA immunoprecipitation, RNA stability measurement and Western blotting were performed to assess the effects of MSI2 on AML. Results We found that MSI2 was significantly overexpressed in AML and exerted its role of promoting AML cell growth by targeting DLL1 and thereby activating Notch signaling pathway. Moreover, we found that MSI2 bound to Snail1 transcript and inhibited its degradation, which in turn upregulated the expression of matrix metalloproteinases. We also found that MSI2 targeting miR-143 is downregulated in AML. In the AML xenograft mouse model, overexpression of MSI2 recapitulated its leukemia-promoting effects, and overexpression of miR-143 partially attenuated tumor growth and prevented metastasis. Notably, low expression of miR-143, and high expression of MSI2 were associated with poor prognosis in AML patients. Conclusions Our data demonstrate that MSI2 exerts its malignant properties via DLL1/Notch1 cascade and the Snail1/MMPs axes in AML, and upregulation of miR-143 may be a potential therapeutic approach for AML.

To address the high complexity and low accuracy issues of traditional methods in mixed coal vitrinite identification, this paper proposes a method based on an improved DeepLabv3+ network. First, MobileNetV2 is used as the backbone network to reduce the number of parameters. Second, an atrous convolution layer with a dilation rate of 24 is added to the ASPP (atrous spatial pyramid pooling) module to further increase the receptive field. Meanwhile, a CBAM (convolutional block attention module) attention mechanism with a channel multiplier of 8 is introduced at the output part of the ASPP module to better filter out important semantic features. Then, a corrective convolution module is added to the network’s output to ensure the consistency of each channel’s output feature map for each type of vitrinite. Finally, images of 14 single vitrinite components are used as training samples for network training, and a validation set is used for identification testing. The results show that the improved DeepLabv3+ achieves 6.14% and 3.68% improvements in MIOU (mean intersection over union) and MPA (mean pixel accuracy), respectively, compared to the original DeepLabv3+; 12% and 5.3% improvements compared to U-Net; 9.26% and 4.73% improvements compared to PSPNet with ResNet as the backbone; 5.4% and 9.34% improvements compared to PSPNet with MobileNetV2 as the backbone; and 6.46% and 9.05% improvements compared to HRNet. Additionally, the improved ASPP module increases MIOU and MPA by 3.23% and 1.93%, respectively, compared to the original module. The CBAM attention mechanism with a channel multiplier of 8 improves MIOU and MPA by 1.97% and 1.72%, respectively, compared to the original channel multiplier of 16. The data indicate that the proposed identification method significantly improves recognition accuracy and can be effectively applied to mixed coal vitrinite identification.

Objectives To identify the clinical phenotypic and molecular pathogeneses of four cases of coagulation factor XII deficiency and to deepen the cognition of this disease.Methods Coagulation tests were performed through one stage of coagulation on a STAGO coagulation analyser. Coagulation factor XII antigen was detected using enzyme-linked immunosorbent assay. The species conservatism and structural change of mutant proteins were analysed using MegAlign and PYMOL. Meanwhile, missense variants and a novel splice site variant were identified using PolyPhen2 and NetGene2.Results The four cases had an observably prolonged activated partial thromboplastin time but without obvious bleeding tendency. Their coagulation factor XII activity (FⅫ:C) and antigen (FXII:Ag) were greatly reduced. Six mutations were detected: NM_000505.4:c.398-1G>A, NP_000496.2:p.(Pro182Leu), NP_000496.2:p.(Ser479Ter), NP_000496.2:p.(Cys559Arg), NC_000005.10:g.7217_7221delinsGTCTA and NM_000505.4:c.1681-1G>A. The first five are newly discovered mutations. The two missense mutation sites were highly conservative, and their protein secondary structure changes may occur not only on the mutation sites but also on other domains. In silico analysis revealed that NP_000496.2:p.(Pro182Leu) may be BENIGN, NP_000496.2:p.(Cys559Arg) may be damaging, and that NM_000505.4:c.398-1G>A and NM_000505.4:c.1681-1G>A are crucial for splicing.Conclusion We found six types of mutations, of which five were novel. The two missense mutation sites might be closely related to the function of coagulation factor XII. The mutations were the primary culprits of factor XII deficiency.

The dynamic landscape of public health occurrences presents a formidable challenge to the emotional well-being of college students, necessitating a precise appraisal of their mental health (MH) status. A pivotal metric in this realm is the Mental Health Assessment Index, a prevalent gauge utilized to ascertain an individual’s psychological well-being. However, prevailing indices predominantly stem from a physical vantage point, neglecting the intricate psychological dimensions. In pursuit of a judicious evaluation of college students’ mental health within the crucible of public health vicissitudes, we have pioneered an innovative metric, underscored by temporal perception, in concert with a hybrid clustering algorithm. This augmentation stands poised to enrich the extant psychological assessment index framework. Our approach hinges on the transmutation of temporal perception into a quantifiable measure, harmoniously interwoven with established evaluative metrics, thereby forging a novel composite evaluation metric. This composite metric serves as the fulcrum upon which we have conceived a pioneering clustering algorithm, seamlessly fusing the fireworks algorithm with K-means clustering. The strategic integration of the fireworks algorithm addresses a noteworthy vulnerability inherent to K-means—its susceptibility to converging onto local optima. Empirical validation of our paradigm attests to its efficacy. The proposed hybrid clustering algorithm aptly captures the dynamic nuances characterizing college students’ mental health trajectories. Across diverse assessment stages, our model consistently attains an accuracy threshold surpassing 90%, thus outshining existing evaluation techniques in both precision and simplicity. In summation, this innovative amalgamation presents a formidable stride toward an augmented understanding of college students’ mental well-being during times of fluctuating public health dynamics.

Abstract It is vital to acquire real‐time pH signals with high resolution as pH variation can reflect important information regarding health status and physiological environment. Field‐effect transistor (FET)‐based biosensors (bio‐FETs), a kind of potentiometric sensor, are being rapidly developed for pH detection due to their advantages of high sensitivity, low temperature dependence, and high portability. More importantly, the high scalability of bio‐FETs renders them applicable for achieving high spatial resolution in pH sensing. In this review paper, the design, operation principle, and critical characteristics of the FET‐based pH sensor are introduced. Then, the recent progress in pH mapping with FET sensor arrays, including static array where a sensor pixel is directly addressed by wiring, and active‐matrix array where a sensor pixel is accessed by additional switching FETs, is presented. Last, typical examples of pH sensor arrays in biomedical applications, such as health monitoring and DNA sequencing and elongation are presented.

Boron neutron capture therapy (BNCT) is a binary modality that is used to treat a variety of malignancies, using neutrons to irradiate boron-10 (10B) nuclei that have entered tumor cells to produce highly linear energy transfer (LET) alpha particles and recoil 7Li nuclei (10B [n, α] 7Li). Therefore, the most important part in BNCT is to selectively deliver a large number of 10B to tumor cells and only a small amount to normal tissue. So far, BNCT has been used in more than 2000 cases worldwide, and the efficacy of BNCT in the treatment of head and neck cancer, malignant meningioma, melanoma and hepatocellular carcinoma has been confirmed. We collected and collated clinical studies of second-generation boron delivery agents. The combination of different drugs, the mode of administration, and the combination of multiple treatments have an important impact on patient survival. We summarized the critical issues that must be addressed, with the hope that the next generation of boron delivery agents will overcome these challenges.

Issues with sentiment analysis in social media include neglecting the long-distance semantic link of emotional features, failing to capture the feature words with emotional hue effectively, and depending excessively on manual annotation. This research provides a user emotion recognition model to achieve the emotional analysis of microblog public opinion events. Three types of inspiring text, “joy,” “anger,” and “sadness,” are obtained by the data collecting and data preprocessing of micro-blog public opinion event comment text. Then, an algorithm using the linear discriminant analysis (LDA) model, emotion dictionary, and manual annotation is created to extract emotional feature words. The captured motivational text is converted into a word vector using Word2vec. After gathering the long-distance semantic data with bidirectional long short-term memories (BiLSTM) and convolutional neural networks (CNN) extract the text’s key characteristics to finish the emotion categorization. The test results demonstrate an average increase in F1 value of 3.66 percent for six machine learning models and an average increase in F1 value of 1.84 percent for seven deep learning models. The suggested model performs better at identifying the emotions of social media users than the current machine learning and deep learning methods.

ObjectiveTo explore the altered expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and cell proliferation index (Ki-67) in primary and metastatic breast cancer lesions and the correlation between the primary tumor size, lymph node metastasis, Tumor Node Metastasis (TNM) stage, molecular typing, and disease-free survival (DFS) and their clinical significance.MethodsA retrospective analysis was conducted on the clinical data of 130 patients with metastatic breast cancer biopsy admitted to the Cancer Center of the Second Affiliated Hospital of Anhui Medical University in Hefei, China, from 2014–2019. The altered expression of ER, PR, HER2, and Ki-67 in primary and metastatic lesions of breast cancer was analyzed with respect to the site of metastasis, size of the primary tumor, lymph node metastasis, disease progression, and prognosis.ResultsThe inconsistent expression rates of ER, PR, HER2, and Ki-67 in primary and metastatic lesions were 47.69%, 51.54%, 28.10%, and 29.23%, respectively. The size of the primary lesion was not, but that accompanied by lymph node metastasis was related to the altered receptor expression. Patients with positive ER and PR expression in both primary and metastatic lesions had the longest DFS, while those with negative expression had the shortest DFS. Also, changes in HER2 expression in primary and metastatic lesions were not associated with DFS. Patients with low expression of Ki-67 in both primary and metastatic lesions had the longest DFS, while patients with high expression had the shortest DFS.ConclusionHeterogeneity was detected in the expression levels of ER, PR, HER2, and Ki-67 in the primary and metastatic breast cancer lesions, which has a guiding significance for the treatment and prognosis of patients.

For patients with end-stage renal disease (ESRD), peritoneal dialysis (PD) and hemodialysis (HD) are important renal replacement treatments. Patients on dialysis usually have a high incidence rate of malignant tumors. In 2020, breast cancer has become the malignant tumor with the highest incidence rate in the world. Human epidermal growth factor receptor-2-positive (HER-2+) breast cancer accounts for 20%-30% of the total breast cancer patients. It is highly invasive and has a poor prognosis. Anti-HER-2 treatment is an important therapy for this type of cancer. There are few case reports of anti-HER2-targeted therapy in dialysis patients. We report a 56-year-old Chinese woman with breast cancer (cT3N1MX, Her-2+/HR-). She underwent peritoneal dialysis for 11 years since she had suffered end-stage renal disease. The clinician prescribed the regimen (pyrotinib 320mg qd + capecitabine 1g bid D1-D14 Q3W). The tumor was significantly reduced after 1 month of single administration of pyrotinib, and partially relieved after 2 months of pyrotinib + capecitabine. The main side effects were grade II hand foot syndrome and grade II diarrhea. This case shows that the combination of pyrotinib and capecitabine has potential therapeutic benefits in HER-2+ breast cancer patients with end-stage renal disease.

BackgroundRecovery of cognitive function after stroke has inter-individual variability. The theory of cognitive reserve offers a potential explanation of the variability in cognitive function after stroke.ObjectiveThis study aimed to investigate the moderating effect of cognitive reserve on the relationship between the stroke severity and cognitive function after stroke.Materials and methodsA total of 220 patients with Acute Ischemic Stroke (AIS) were recruited in 2021 from two stroke centers in Nanjing, China. The National Institutes of Health Stroke Scale (NIHSS) was used to assess stroke severity upon admission. Cognitive Reserve Index questionnaire (CRIq) and validated Montreal Cognitive Assessment, Changsha Version (MoCA-CS) were used to assess cognitive reserve and cognitive function within 7 days after stroke onset, respectively. A series of multivariate linear regression models were applied to test the moderating effect of cognitive reserve.ResultsPatients with a higher level of cognitive reserve had better cognitive function after stroke compared with those with a lower level of cognitive reserve (β = 0.074, p = 0.003). The interaction of NIHSS and cognitive reserve was statistically significant (β = −0.010, p = 0.045) after adjusting for some key covariates [e.g., age, marital status, Oxfordshire Community Stroke Project (OCSP) classification, Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification, cerebral vascular stenosis, diabetes and atrial fibrillation].ConclusionCognitive reserve may help to buffer the effect of stroke-related pathology on cognitive decline in Chinese acute stroke patients. Enhancing cognitive reserve in stroke patients may be one of the potential strategies for preventing vascular dementia.

BackgroundChimeric antigen receptor T (CAR-T) cell therapy has made significant advances for hematological malignancies but encounters obstacles in the treatment of solid tumors mainly due to tumor immunosuppressive microenvironment.MethodsImmunohistochemistry analysis was performed to examine the cellular expression of nectin cell adhesion molecule-4 (Nectin4) and fibroblast activation protein (FAP) in a variety of malignant solid tumors. Then, we engineered the fourth-generation Nectin4-targeted CAR-T (Nectin4-7.19 CAR-T) and FAP-targeted CAR-T (FAP-12 CAR-T) cells to evaluate their safety and efficacy in vitro and in vivo.ResultsIn our study, we firstly demonstrated the aberrant overexpression of Nectin4 on both primary and metastatic solid tumors and FAP on cancer-associated fibroblasts. Then, we found that our fourth-generation Nectin4-7.19 CAR-T cells expressed IL-7 and CCL19 efficiently and exhibited superior proliferation, migration, and cytotoxicity compared to the second-generation Nectin4 CAR-T cells, while FAP-12 CAR-T cells exerted their ability of targeting both murine and human FAP effectively in vitro. In a fully immune-competent mouse model of metastatic colorectal cancer, lymphodepletion pretreated mice achieved complete remission with human Nectin4-targeted murine CAR-T (Nectin4 mCAR-T) cells. In the NSG mouse model of lung metastases, Nectin4-7.19 CAR-T cells eradicated metastatic tumors and prolonged survival in combination with FAP-12 CAR-T cells.ConclusionsThese findings showed that Nectin4-7.19 CAR-T cells had potential therapeutic efficacy and exerted a synergistic role with FAP-12 CAR-T cells, further demonstrating that Nectin4 and FAP were able to serve as promising targets for safe and effective CAR-T therapy of malignant solid tumors.

Claystone is potentially the main rock formation for the deep geological disposal of high-level radioactive nuclear waste. A major factor that affects the deformation of the host medium is effective stress. Therefore, studying the effective stress principle of claystone is essential for a stability analysis of waste disposal facilities. Consolidated drained (CD) tests were carried out on claystone samples to study their effective stress principle in this paper. Firstly, two samples were saturated under a specified confining pressure and pore pressure for about one month. Secondly, the confining pressure and pore pressure were increased to a specified value simultaneously and then reverted to the previous stress state (the deformations of the samples were recorded during the whole process). Different incremental combinations of the confining pressure and pore pressure were tried at this step. Finally, the effective stress coefficients of the samples were obtained through a back analysis. Furthermore, some potential influencing factors (the neutral stress and loading rate) of the effective stress coefficient were also studied through additional tests. Some interesting results are worth mentioning: (1) the effective stress coefficient of claystone is close to one; (2) the neutral stress and loading rate may have little effect on the effective stress coefficient of claystone.

Abstract Memristors based neuromorphic devices can efficiently process complex information and fundamentally overcome the bottleneck of traditional computing based on von Neumann architecture. Meanwhile, natural biomaterials have attracted significant attention for biologically integrated electronic devices due to their excellent biocompatibility, mechanical flexibility, and controllable biodegradability. Thus, biomaterial‐based memristors may have a transformative impact on bridging electronic neuromorphic systems and biological systems. However, the working voltage in biological system is low, but the operation voltages of conventional memristors are high, violating the energy‐efficient biological system. Here, high‐performance silk fibroin‐based threshold switching (TS) memristors are demonstrated, which reveal an on‐current of 1 mA, a low threshold voltage (Vth) of 0.17 V, a high selectivity of 3 × 106, and a steep turn‐on slope of

ObjectiveTo explore the correlation between HER-2 status and pathological complete response (pCR) in HER-2-positive breast cancer after dual anti-HER-2 neoadjuvant therapy with trastuzumab and pertuzumab.MethodsA total of 57 HER-2-positive breast cancer patients admitted to the Second Affiliated Hospital of Anhui Medical University and Xijing Hospital Affiliated to Air Force Military Medical University, between January 1, 2019 and September 30, 2020, were enrolled in this multicenter retrospective study. HER-2 status, including HER-2/CEP17 ratio and HER-2/cell number ratio, was detected by FISH. The correlation between HER-2 status/clinicopathological data and pCR was analyzed. The ROC curve was drawn to determine the cutoff value.ResultsIHC assessment revealed 40 (70.18%) patients with IHC 3+ and 17 (29.82%) with IHC 2+. 41/57 (71.93%) patients achieved pCR. FISH revealed that the ratio of HER-2/chromosome 17 centromere (HER-2/CEP17) (p

Summary: Flexible biosensors have received intensive attention for real-time, non-invasive monitoring of cancer biomarkers. Highly sensitive tyrosinase biosensors, which are important for melanoma screening, remained a hurdle. Herein, high-performance tyrosinase-sensing field-effect transistor-based biosensors (bio-FETs) have been successfully achieved by self-assembling nanostructured tetrapeptide tryptophan–valine–phenylalanine–tyrosine (WVFY) on n-type metal oxide transistors. In the presence of target tyrosinase, the phenolic hydroxyl groups in WVFY are rapidly converted to benzoquinone with the consumption of protons, which could be detected potentiometrically by bio-FETs. As a result, the WVFY-modified bio-FETs exhibited an ultra-low detection limit of 1.9 fM and an optimal detection range of 10 fM to 1 nM toward tyrosinase sensing. Furthermore, flexible devices fabricated on ∼2.9-μm-thick polyimide (PI) substrates illustrated robust mechanical flexibility, which could be attached to human skin conformally. These achievements hold promise for wearable melanoma screening and provide designing guidelines for detecting other important cancer biomarkers with bio-FETs.

A new method of replacing soft soil with lightweight foam concrete (lightweight foam concrete replacement method, LFCRM) is carried out to treat deep soft foundation under the low-filled embankment. Two-dimensional models with different thicknesses of replacement are established by the finite element platform (MIDAS/GTS). Moreover, the deformation and stress distribution law of treated foundation is analyzed by numerical simulation with different models. The results are as follows: (1) LFCRM can offset part of dead load; (2) the transverse distribution of settlement presents an “arc” shape; (3) the replacement made of lightweight foam concrete can spread stress well; (4) increase of replacement thickness will cause the necking of the additional stress “bubble”; (5) initial excess pore water pressure is related to the additional stress, and its dissipation path is deduced; (6) preliminary analysis indicates the feasibility of LFCRM for treating deep soft foundation with the low-filled embankment.

Abstract The practice of eating insects has been documented for a long time. With obvious economic and environmental advantages, edible insects are in the spotlight recently due to their enormous potential in multiple industries. A number of research has been conducted to maximize their value, but concerns have been raised for the food security. In this review, we compared the characteristics of edible insects with other traditional protein sources. The progress of modern entomophagy was introduced. The benefits and risks of eating insects were summarized. Additionally, the shortcoming of current production were discussed. Feasible ways and strategies were proposed to promote the consumption of edible insects. Graphical abstract

Coagulation factor XII (FXII) plays a crucial role in thrombosis. Moreover, deficiencies in FXII are not associated with excessive bleeding, and its depletion exhibits satisfactory protective effect on thrombus formation. Several strategies targeting FXII have been applied to inhibit thrombosis formation. In this study, C57BL/6 mice were injected with adeno-associated virus (AAV) to identify the role of short hairpin RNA (shRNA) in thrombosis. Differences in liver FXII, coagulation function, and thrombus formation were detected. The potential side effects of FXII were then evaluated through analysis of tail bleeding, biochemical indices, and pathological sections. Results showed that shRNAs, especially shRNA2, carried by AAV, effectively reduced the expression of FXII. Furthermore, only shRNA2 demonstrated an anti-thrombosis effect on multiple models without hemorrhage and side effects. Hence the novel approach of AAV-based shRNA is specific and safe for inhibiting FXII and thrombosis.

Background and objective Adipocytes in the tumor microenvironment may provide the metabolic fuel or signal transduction through media and other means to promote a variety of malignant proliferation and invasion, of tumor cells, but their role in lung cancer progression is still unclear. The purpose of this study was to investigate the effect of adipocytes on lung cancer cell biology. Methods 3T3-L1 pre-adipocytes were induced into mature adipocytes. The cell morphology was observed by microscopy and Oil Red O staining. MTT assay, colony formation assay, wound-healing and Transwell methods were used to detect lung cancer cell proliferation, migration and invasion ability. The content of triglyceride in cells was determined by colorimetry. Results The morphology of lung adenocarcinoma A549 cells became more slender after co-culture with mature adipocytes, and the proliferation and cloning ability were significantly enhanced (P

Recurrent miscarriage is defined as the loss of 3 or more consecutive pregnancies; however, the underlying immunologic mechanisms that trigger pregnancy loss remain largely unelucidated. Galectin-9 (Gal-9) may modulate a variety of biologic functions and play an important role in Th1/Th2 immune deviation. To analyze the mechanism of Gal-9 in abortion, we used the classical abortion-prone mouse model (DBA/2-mated CBA/J mice) to detect the expression of Gal-9 at the maternal-fetal interface. We also mimicked the immune environment of pregnancy by culturing trophoblast cells with peripheral blood mononuclear cells (PBMCs) to explore how Gal-9 might be involved in the pathogenesis of abortion. We found that the expression levels of Gal-9 in abortion-prone matings were lower than that for controls. Using a coculture system, we detected a Th1 preponderance in the coculture from abortion-prone matings. Furthermore, Gal-9 blockade augmented the imbalance of Th1/Th2 immunity in abortion-prone matings by promoting the secretion of Th1-derived cytokines in coculture, while there was a Th2 preponderance when we administered recombinant Gal-9. In conclusion, our results suggest that the Gal-9 signal is important for the regulation of PBMC function toward a Th2 bias at the maternal-fetal interface, which is beneficial for the maintenance of a normal pregnancy.

We study the existence and uniqueness of the solutions for the boundary value problem of fractional differential equations with nonlinear boundary conditions. By using the upper and lower solutions method in reverse order and monotone iterative techniques, we obtain the sufficient conditions of both the existence of the maximal and minimal solutions between an upper solution and a lower solution and the uniqueness of the solutions for the boundary value problem and present the iterative sequence for calculating the approximate analytical solutions of the boundary value problem and the error estimate. An example is also given to illustrate the main results.

In this work, we investigate the existence and non-existence of traveling wave solutions for a chemotaxis model with two chemoattractants. To prove our main results, we apply the dynamical systems theory by constructing a positively invariant set in the four-dimensional space. Particularly, we analyze the monotonicity of traveling wave solutions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Progressive resistance inspiratory muscle training is the principle of inspiratory air-flow resistance loading training to restore diaphragm function, increase alveolar compliance, and further improve respiratory function. However, there is a lack of research on the effectiveness of progressive resistance inspiratory training in post-lobectomy rehabilitation and the accurate assessment of lung volumes. METHODS: In this study, 79 subjects diagnosed with lung cancer and undergoing thoracoscopic lobectomy were retrospectively analyzed. The subjects were divided into a control group (n = 40) and an observation group (n = 39) according to the different training modalities. The control group received conventional respiratory training. The observation group received progressive resistance inspiratory muscle training based on conventional breathing training. The primary outcome indicators were the following: lung function and lung volume. The secondary outcome indicators were the following: the number of postoperative hospital days, duration of drain retention, and incidence of postoperative pulmonary complications. RESULTS: Baseline data on age, sex, body mass index, smoking history, education level, underlying disease, type of pathology, lung cancer stages, surgical site, preoperative lung volume, and preoperative lung function were not statistically different between the 2 groups (P > .05). The subjects in the observation group had median (interquartile range [IQR]) lung volumes at 1 month after surgery (3.22 [3.12-3.37] L vs 3.14 [2.95-3.24] L; P = .031), median (IQR) FEV1 (2.11 [1.96-2.21] L vs 2.01 [1.81-2.12] L; P = .031), and mean 6 SD peak expiratory flow (5.07 ± 0.62 L/s vs 4.66 ± 0.64 L/s; P = .005) were higher than those in the control group. The median (IQR) postoperative hospital stays (5 [4-5] d vs 5 [4-6] d; P = .030) and the median (IQR) chest drain retention times were shorter in the observation group versus the control group (74 [72-96] h vs 96 [84-96] h; P = .02). There was no significant difference in the incidence of postoperative atelectasis (5.1% vs 10.0%; P = .41) and pneumonia (7.7% vs 12.5%; P = .48). CONCLUSIONS: Progressive resistance inspiratory muscle training was effective in improving lung volume and lung function, and in reducing the length of hospital stay and chest drain closure time after lobectomy. [ABSTRACT FROM AUTHOR]